The long-term objective of the proposed studies is to develop a rapidly effective safe method for dissolving cholesterol gallstones in the gallbladder and bile ducts. A new cholesterol solvent, methyl tertiary-butyl ether (MTBE), has been evaluated in vitro and in dogs and found to be extremely effective and safe. Initial feasibility studies in humans have been well tolerated and multiple gallstones in the gallbladder have been dissolved within seven hours. The major specific aim of this proposal is to determine the safety and efficacy of MTBE as a solvent for cholesterol gallstones in the gallbladder in 60 patients and in the bile ducts in 15 patients. A second objective is to further refine the methodology for the use of direct contact stone solvents in the biliary tract. The predominant methodology will utilize percutaneous transhepatic catheterization of the gallbladder but means for retrograde catheterization of the cystic duct will be explored. Technology for efficient removal of bile and stirring or exchange of the solvent will be assessed and further refined. Because 16 to 20 million patients in the United States have cholesterol gallstones, a rapidly effective safe treatment would offer an important therapeutic advance for those in need of intervention.